The comparative pharmacokinetics of pentamethylmelamine in man, rat, and mouse.
The pharmacokinetics of pentamethylmelamine (PMM) have been investigated in mouse (Balb C-, CBA/LAC, nude), rat (Wistar), and man. In all three species, PMM was extensively demethylated to N2,N2,N4,N6-tetramethylmelamine and N2,N4,N6-trimethylmelamine, although marked species differences in the rate of metabolism were observed. PMM metabolism was more rapid in the mouse (plasma t1/2 = less than 15 min) than in the rat (plasma t1/2 = 40 min), and slower in man (plasma t1/2 = 102 min) than in either mouse or rat. Furthermore, the peak plasma concentrations of N-methylolmelamines, intermediates generated during oxidative N-demethylation, were correspondingly higher in the mouse (563-773 microM) than in the rat (211 microM), whilst in man they were undetectable (less than 50 microM). In view of the highly cytotoxic nature of N-methylolmelamines, we conclude that these pharmacokinetic differences may be related to the antitumour effectiveness of PMM in mouse, rat, and man.
D006585:Altretamine / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism; D013045:Species Specificity; D014227:Triazines / Q000378:metabolism*
D000970:Antineoplastic Agents; D014227:Triazines; D006585:Altretamine; C022048:pentamethylmelamine